Paternal heroin self-administration in rats increases drug-seeking behavior in male offspring via miR-19b downregulation in the nucleus accumbens

Neuropsychopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 8, 2025

Abstract Accumulating evidence indicates that drug addiction may lead to adaptive behavioral changes in offspring, potentially due epigenetic modifications parental germline. However, the underlying mechanisms remain inadequately understood. In this study, we show paternal heroin self-administration (SA) increased heroin-seeking behavior F1 generation, when compared with offspring sired by yoke-infused control males, indicating cross-generational impact of voluntary seeking behavior. Notably, increase was replicated zygotic microinjection sperm RNAs derived from heroin-SA-experienced rats. Analysis non-coding spermatozoa revealed coordinated miRNA content between nucleus accumbens and spermatozoa. We validated restoration miR-19b downregulation RNA self-administration-experienced rats, parallel its overexpression fathers, reversed SA observed these offspring. Taken together, our findings suggest rats induces both brain miRNA, playing a critical role mediating inheritance generation.

Language: Английский

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Analgesic Peptides: From Natural Diversity to Rational Design

Molecules, Journal Year: 2024, Volume and Issue: 29(7), P. 1544 - 1544

Published: March 29, 2024

Pain affects one-third of the global population and is a significant public health issue. The use opioid drugs, which are strongest painkillers, associated with several side effects, such as tolerance, addiction, overdose, even death. An increasing demand for novel, safer analgesic agents driving force exploring natural sources bioactive peptides antinociceptive activity. Since G protein-coupled receptors (GPCRs) play crucial role in pain modulation, discovery new peptide ligands GPCRs challenge novel drug development. aim this review to present human animal origin potential show possibilities their modification, well design structures. study presents current knowledge on structure-activity relationship peptide-based biomimetic compounds, modification strategies directed at activity, improvement metabolic stability pharmacodynamic profile. procedures employed prolonged delivery emerging compounds also discussed. work summarizes conditions leading development morphine replacements.

Language: Английский

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Differential involvement of neurotransmitter pathways in AD, bvFTD and MCI: Whole-brain MRI analysis

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106897 - 106897

Published: April 1, 2025

Neurodegenerative diseases, including Alzheimer's disease (AD), mild cognitive impairment (MCI), and frontotemporal dementia (FTD), are a growing public health challenge, with incidence projected to triple in the coming decades. AD is associated memory impairment, bvFTD behavioral dysfunction, MCI as transitional stage between normal cognition dementia. While structural brain changes have been widely studied, role of neurotransmitter pathways remains underexplored. This study aims correlate gray matter atrophy AD, bvFTD, identify distinctive neurochemical impairments. We included 214 participants (89 CE, 74 51 MCI) from single-center cohort. MRI 3 T scanners was segmented via FreeSurfer. Neurotransmitter maps were sourced JuSpace. performed volumetric whole-brain correlation analyses evaluate relationships regional volumes (BRVs) pathways. Group differences assessed Kruskal-Wallis tests followed by post-hoc analyses. Volumetric analysis showed expected patterns each group. Correlation indicated distinct involvement: significant correlations dopamine D2 GABA A receptor distribution; had negative mu-opioid receptor; exhibited early serotonergic dysregulation. identified linked specific systems, showing unique profiles. In precuneus inferior parietal lobules aligns dopaminergic GABAergic receptors, potentially impacting executive functions. medial orbitofrontal temporal atrophy, possibly contributing symptoms. MCI, dysregulation involving SERT occurs before detectable atrophy.

Language: Английский

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Treatment of dissociative identity disorder: leveraging neurobiology to optimize success

Expert Review of Neurotherapeutics, Journal Year: 2024, Volume and Issue: 24(3), P. 273 - 289

Published: Feb. 15, 2024

Dissociative identity disorder (DID) is a treatable mental health condition that associated with range of psychobiological manifestations. However, historical controversy, modern day misunderstanding, and lack professional education have prevented accurate treatment information from reaching most clinicians patients. These obstacles also slowed empirical efforts to improve outcomes for people DID. Emerging neurobiological findings in DID provide essential can be used outcomes.

Language: Английский

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A mammalian tripartite enhancer cluster controls hypothalamic Pomc expression, food intake, and body weight

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(18)

Published: April 23, 2024

Food intake and energy balance are tightly regulated by a group of hypothalamic arcuate neurons expressing the proopiomelanocortin ( POMC) gene. In mammals, arcuate-specific POMC expression is driven two cis -acting transcriptional enhancers known as nPE1 nPE2. Because mutant mice lacking these still showed Pomc mRNA, we searched for additional elements contributing to expression. By combining molecular evolution with reporter gene in transgenic zebrafish mice, here, identified mammalian enhancer that named nPE3, carrying several binding sites also present nPE2 transcription factors activate neuronal expression, such ISL1, NKX2.1, ERα. We found nPE3 originated lineage leading placental mammals remained under purifying selection all orders, although it was lost Simiiformes (monkeys, apes, humans) following unique segmental deletion event. Interestingly, ablation from mouse genome led drastic reduction (>70%) mRNA during development only moderate (<33%) adult mice. Comparison between double (nPE1 nPE2) triple (nPE1, nPE2, nPE3) mutants revealed relative contribution its importance control food adiposity male female Altogether, results demonstrate integrates tripartite cluster partially redundant upon convergent evolutionary process critical body weight homeostasis.

Language: Английский

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Endogenous Opioid Peptides After Floatation Therapy in Resistance-Trained Men

The Journal of Strength and Conditioning Research, Journal Year: 2024, Volume and Issue: 38(10), P. 1808 - 1812

Published: Oct. 1, 2024

Kraemer, WJ, Caldwell, LK, Post, EM, Volek, JS, Hagen, JM, Newton, RU, Häkkinen, K, Omonije, O, and Maresh, CM. Endogenous opioid peptides after floatation therapy in resistance trained men. J Strength Cond Res 38(10): 1808-1812, 2024-Floatation-restricted environmental stimulation (Float-REST) has shown improvements muscle soreness fatigue. To determine whether float influences the release of beta-endorphin (β-End) proenkephalin (ProEnk) acute heavy exercise, 11 healthy resistance-trained men (age: 22.5 ± 2.3 years; height: 176.4 6.0 cm; body mass: 85.7 6.2 kg, back squat one-repetition maximum: 153.1 20.1 kg; strength-to-mass ratio: 1.8 0.2) completed a within-subject, cross-over controlled study design. Subjects 2 exercise testing blocks separated by 2-week washout. In one block, 1-hour session followed high-intensity protocol (6 × 10 squats at 80% 1RM, minutes rest). By contrast, recovery alternate block consisted passive sensory-stimulating control. Blood samples were collected 5 time points-before immediately after1-hour treatment, 24 hours 48 exercise. Samples analyzed duplicate for β-End ProEnk using ELISA immunoassays. Mean differences assessed repeated-measures ANOVA. Plasma demonstrated expected significant (p ≤ 0.05) increase following both treatment conditions. There no changes with stress precursor peptide. The absence differential Float-REST suggests that these may not underlie deep relaxation experiences commonly reported this intervention However, practically, it shows remains consistently similarly increased to stress. concentrations are detectable stable but do respond workout protocol, which, as primary peptide precursor, paracrine cybernetics circulation exist.

Language: Английский

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Técnicas não farmacológicas para redução de ansiedade entre parturientes submetidas ao parto normal: uma revisão sistemática

Research Society and Development, Journal Year: 2022, Volume and Issue: 11(5), P. e2511527921 - e2511527921

Published: March 28, 2022

Objetivo: Analisar as principais técnicas não farmacológicas para redução de ansiedade entre parturientes submetidas ao parto normal. Metodologia: Trata-se uma revisão sistemática realizada por meio do método PRISMA, nas bases dados eletrônicas PubMed, Scopus e Web of Science, dos seguintes descritores: “pregnancy”, “parturition”, “natural childbirth”, “anxiety”, “therapeutics” “complementary therapies”. Foram incluídos artigos completos, disponíveis em português, inglês ou espanhol, publicados janeiro 2016 a dezembro 2021 que fornecessem descrição detalhada das intervenções da mulheres Resultados: 11 compuseram amostra final deste estudo, com maior frequência publicação (n: 04) produção Irã Brasil 03). Todas pesquisas utilizaram metodologia Ensaio Clínico Randomizado Controlado, caracterizando como apresentando nível evidência forte (II). As mais utilizadas foram: aromaterapia 04), hidroterapia ducha quente exercícios perineais bola 02), musicoterapia respiração 02) massagem 01). Os períodos destas variaram 10 minutos 2 horas, na duração 30 minutos. Conclusão: Verificou-se seis demonstraram reduzir normal, diferentes tamanhos efeitos, especialmente musicoterapia.

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Nalbuphine and Addiction: From the Basic Science to Clinical Set

Journal of Clinical Research in Anesthesiology, Journal Year: 2019, Volume and Issue: 2(2)

Published: Jan. 1, 2019

The use of opioids, especially morphine, has been the main choice for analgesia in moderate to severe pain.Nalbuphine (C 21 H 27 NO 4 ) is a synthetic kappa-receptor agonist and partial mu-receptor antagonist opioid drug, available approved use, designated an attempt provide without undesirable side effects pure mu-opioids agonists like morphine.The possibility using nalbuphine as alternative drug view increasing worldwide addiction/dependence rates therefore alarming overdose deaths seems rational option due its favorable pharmacological profile terms adverse equivalent analgesic potential.Thus, we performed literature review past 10 years evaluate basic clinical scientific evidence about potential role current scenario addiction dependence on opioids.

Language: Английский

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Efeitos da nalbufina e do tramadol após infusão contínua com fentanil em cães submetidos a osteotomia de nivelamento de platô tibial (TPLO)

Published: April 6, 2016

Efeitos da nalbufina e do tramadol após infusão contínua com fentanil em cães

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Aspectos neuroimunes de camundongos tratados com morfina.

Published: June 17, 2010

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